Effects of ciprofloxacin concentrations on the resistance of uropathogen Escherichia coli: in vitro kinetics and dynamics simulation mode

https://doi.org/10.19106/JMedSci005203202001

Maya Dian Rakhmawatie(1*), . Mustofa(2), Eti Nurwening Sholikhah(3)

(1) Departement of Biomedical Sciences, Faculty of Medicine, Universitas Muhammadiyah Semarang, Semarang, Indonesia
(2) Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(3) Department of Pharmacology and Therapy, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
(*) Corresponding Author

Abstract


Ciprofloxacin is recommended for complicated urinary tract infection (UTIs) caused by multidrug-resistant pathogens included Escherichia coli. However, its optimum dose for UTIs remains uncertain that may cause the bacterial resistance. This study was conducted to evaluate the effects of ciprofloxacin concentrations on the resistance of E. coli. The in vitro pharmacokinetic/pharmacodynamic (PK/PD) models of ciprofloxacin 750 mg oral dose twice a day for one daywas compared to that dose of 500 mg twice a day for three days.Pharmacokinetic parameters i.e.AUC0-24 and Cmax. and pharmacodynamic parameter i.e. MIC of ciprofloxacin against E. coli which previously had MIC of 0.5 µg/mL were determined. The PK/PD parameters combination of ciprofloxacin included AUC0-24/MIC, Cmax/MIC, and T>MIC ratio were used to evaluate its antimicrobial activities which was measured based on kill and re-growth rates of bacterial colony after the ciprofloxacin administration. The result showed that MIC value against E. coli increase to 8-16 and 32-64 µg/mL after ciprofloxacin 750 and 500 mg administration, respectively, indicating the emergence of resistance. Both doses of ciprofloxacin were able to reduce the number of bacterial colony in the first two hours administration. However, after two hours administration, those both doses could make re-growth of bacterial colony. The value of AUC0-24/MIC (120.42±1.27 vs.92.62±9.36), Cmax/MIC (4.75±0.21 vs. 3.26±0.30), and (T>MIC 89.58±7.22 vs. 76.39±9.39) after ciprofloxacin administration at dose of 750 mg were higher than those at dose of 500 mg. The increase of AUC0-24/MIC and Cmax/MIC values could reduce the number of bacteria colony, however could not for T>MIC value. In conclusion, the AUC0-24/MIC and Cmax/MIC parameters of ciprofloxacincan be used to evaluate its activity. In addition, ciprofloxacin twice per day at dose 500 mg for three days and 750 mg for one day are not different in the inhibition of E. coli resistance emergence.


Keywords


ciprofloxacin; pharmacokinetic; pharmacodynamics-E.coli; resistance;

Full Text:

PDF


References

  1. Drusano GL. Pharmacokineticsand pharmacodynamics of antimicrobial.Clin Infect Dis2007; 45(1):89-95. https://doi.org/10.1086/518137
  2. Onufrak NJ, Forrest A, Gonzales D. Pharmacokinetic and pharmacodynamic principles of anti-infectivedosing. Clin Ther 2016; 38(9):1930-47. https://doi.org/10.1016/j.clinthera.2016.06.015
  3. Gloede J, Scheerans C, Derendorf H, Kloft C. In vitro pharmacodynamic models to determine the effect of antibacterial drugs. J Antimicrob Chemother 2010; 65(2):186-201. https://doi.org/10.1093/jac/dkp434
  4. Zhao M, Lepak AJ, Andes DR. Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents. Bioorg Med Chem 2016; 24(1):6390-400. https://doi.org/10.1016/j.bmc.2016.11.008
  5. Dudley MN, Griffith D. Animal models of infection for the study of antibiotic pharmacodynamics. In: Nightingale CH, Murakawa T, Ambrose PG, eds. Antimicrobial Pharmacodynamics in Theory and Clinical Practice. New York: Marcel Dekker, Inc., 2002: 67–98.
  6. McLain JE, Cytryn E, Durso LM, Young S. Culture-basedmethods for detection of antibiotic resistance in agroecosystems: advantages, challenges, and gaps in knowledge. J Environ Qual 2016; 45(Special Section):432-40. https://doi.org/10.2134/jeq2015.06.0317
  7. Hooton TM. Uncomplicated urinary tract infection. N Eng J Med 2012; 366(11):1028-37. https://doi.org/10.1056/NEJMcp1104429
  8. White B. Diagnosis and treatment of urinary tract infections in children. Am Fam Physician 2011; 83(4):409-15.
  9. Colgan R, Willians M. Diagnosis and treatment of acute pyelonephritis in women. Am Fam Physician 2011; 84(5):519-26.
  10. Committee on Infectious Diseases. The use of systemic fluoroquinolones. Pediatrics 2006; 118(3):1287-92. https://doi.org/10.1542/peds.2006-1722
  11. Shoff WH, Green-McKenzie J, Edwards C, Behrman AJ, Shepherd SM. Acute pyelonephritis: the differential diagnosis and workup.March 5, 2010. [cited 2013, June 17] Available from: http://emedicine.medscape.com/article/245559.
  12. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan C, Miller LG, et al. International clinical practice guideline for the treatment of acute uncomplicated cystitisand pyelonephritis in woman: a 2010 update by the infectious disease society of america and the european society for microbiology and infectious disease. Clin Infect Dis 2011; 52(5):103-20. https://doi.org/10.1093/cid/ciq257
  13. Milo G, Katchman E, Paul M, Christiaens T, Baerheim A, Leibovici L. Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane Database Syst Rev 2005; 18(2):004682. https://doi.org/10.1002/14651858.CD004682.pub2
  14. Lutters M, Vogt‐Ferrier NB. Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women. Cochrane Database Syst Rev 2008; 19(4): 001535. https://doi.org/10.1002/14651858.CD001535.pub2
  15. Fantin B, Duval X, Massias L, Alavoine L, Chau F, Retout S, et al. Ciprofloxacin dosage and emergence of resistance in human comensal bacteria. J Infect Dis 2009; 200(3):390-8. https://doi.org/10.1086/600122
  16. Khan DD, Lagerbak P, Cao S, Lustig U, Nielsen EI, Cars O, et al. A mechanism-based pharmacokinetic/pharmacodynamic model allows prediction of antibiotic from MIC values for WT and mutants. J Antimicrob Chemother 2015; 70(11):3051-60. https://doi.org/10.1093/jac/dkv233
  17. Reygaert W. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbil 2018; 4(3):482-501. https://doi.org/10.3934/microbiol.2018.3.482
  18. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr 2016; 4(2):10.1128/microbiolspec.VMBF-0016-2015 https://doi.org/10.1128/microbiolspec.VMBF-0016-2015
  19. Andersson DI, Hughes, D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 2010; 8(4):260-71. https://doi.org/10.1038/nrmicro2319
  20. Vander Horst MA, Schuurmans JM, Smid MC, Koenders BB, ter Kuile BH. De novo acquisition of resistance to three antibiotics by Escherichia coli. Microb Drug Resist 2011; 17(2):141-7. https://doi.org/10.1089/mdr.2010.0101
  21. Novelli A, Rosi E. Pharmacological properties of oral antibiotics for the treatment of uncomplicated urinary track infections. J Chemother 2017; 29(1):10-8. https://doi.org/10.1080/1120009X.2017.1380357
  22. Peloquin CA, Cumbo TJ, Nix DE, Sand MF, Schentag JJ. Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infection, Impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication. Arch Intern Med 1989; 149(10):2269-73.
  23. Thomas JK, Forrest A, Bhavnani SM, Hyatt JM, Cheng A, Ballow CH, et al. Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy.Antimicrob Agents Chemother 1998; 42(3):521-7.
  24. Craig WA. Does the dose matter? Clin Infect Dis 2001; 33 (Suppl.3):S233-7.
  25. Zelenitsky SA& Ariano RE. Support for higher ciprofloxacin AUC0-24/MIC targets in treating Enterobacteriacea bloodstream infection. J Antimicrob Chemother 2010; 65(1):1725-32. https://doi.org/doi:10.1093/jac/dkq211



DOI: https://doi.org/10.19106/JMedSci005203202001

Article Metrics

Abstract views : 1247 | views : 1603


Bookmark and Share


Copyright (c) 2020 Maya Dian Rakhmawatie, . Mustofa, Eti Nurwening Sholikhah

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats

 

Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Based on a work at http://jurnal.ugm.ac.id/bik/.